IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish
MyD88 is a conserved intracellular adaptor, which plays an important role in the innate immune system. MyD88 transmits signals for downstream of toll-like and IL-1 receptors to activate NF-κB signaling pathway, which is tightly controlled in the immune response to maintain immune intensity and immun...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00606/full |
| _version_ | 1818559966179491840 |
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| author | Xiaolong Yan Xiaolong Yan Xueyan Zhao Ruixuan Huo Tianjun Xu Tianjun Xu Tianjun Xu Tianjun Xu Tianjun Xu |
| author_facet | Xiaolong Yan Xiaolong Yan Xueyan Zhao Ruixuan Huo Tianjun Xu Tianjun Xu Tianjun Xu Tianjun Xu Tianjun Xu |
| author_sort | Xiaolong Yan |
| collection | DOAJ |
| description | MyD88 is a conserved intracellular adaptor, which plays an important role in the innate immune system. MyD88 transmits signals for downstream of toll-like and IL-1 receptors to activate NF-κB signaling pathway, which is tightly controlled in the immune response to maintain immune intensity and immune homeostasis at different stages. NF-κB signaling pathway has been extensively studied in mammals, but regulatory molecular mechanism is still unclear in teleost fish. We determined that IRF3 and IRF8 can regulate MyD88-mediated NF-κB signaling pathway in fish. Interestingly, MyD88 is precisely regulated by IRF3 and IRF8 through the same mechanism but in completely opposite ways. IRF3 promotes MyD88-mediated NF-κB signaling pathway, whereas IRF8 inhibits the signaling pathway. MyD88 is regulated via ubiquitin–proteasome degradation, whereas IRF3 or IRF8 inhibited or promoted MyD88 degradation in this pathway. Specifically, in the early stage of lipopolysaccharide (LPS) stimulation or Vibrio infection, up-regulation of IRF3 and down-regulation of IRF8 eventually increased MyD88 expression to activate the NF-κB signaling pathway to trigger immune response. In the late stage of stimulation, down-regulated IRF3 and up-regulated IRF8 synergistically regulate the expression of MyD88 to a normal level, thus maintaining the immune balance of homeostasis and preventing serious damage from persistent over-immunization. This study presents information on Myd88–NF-κB signaling pathway in teleost fish and provides new insights into its regulatory mechanism in fish immune system. |
| first_indexed | 2024-12-14T00:32:23Z |
| format | Article |
| id | doaj.art-d33adca7330f46a483eef5081e87cf7a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T00:32:23Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d33adca7330f46a483eef5081e87cf7a2022-12-21T23:24:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-04-011110.3389/fimmu.2020.00606527468IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost FishXiaolong Yan0Xiaolong Yan1Xueyan Zhao2Ruixuan Huo3Tianjun Xu4Tianjun Xu5Tianjun Xu6Tianjun Xu7Tianjun Xu8Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, ChinaLaboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, ChinaLaboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, ChinaLaboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, ChinaLaboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, ChinaLaboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, ChinaNational Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai, ChinaKey Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, ChinaInternational Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, ChinaMyD88 is a conserved intracellular adaptor, which plays an important role in the innate immune system. MyD88 transmits signals for downstream of toll-like and IL-1 receptors to activate NF-κB signaling pathway, which is tightly controlled in the immune response to maintain immune intensity and immune homeostasis at different stages. NF-κB signaling pathway has been extensively studied in mammals, but regulatory molecular mechanism is still unclear in teleost fish. We determined that IRF3 and IRF8 can regulate MyD88-mediated NF-κB signaling pathway in fish. Interestingly, MyD88 is precisely regulated by IRF3 and IRF8 through the same mechanism but in completely opposite ways. IRF3 promotes MyD88-mediated NF-κB signaling pathway, whereas IRF8 inhibits the signaling pathway. MyD88 is regulated via ubiquitin–proteasome degradation, whereas IRF3 or IRF8 inhibited or promoted MyD88 degradation in this pathway. Specifically, in the early stage of lipopolysaccharide (LPS) stimulation or Vibrio infection, up-regulation of IRF3 and down-regulation of IRF8 eventually increased MyD88 expression to activate the NF-κB signaling pathway to trigger immune response. In the late stage of stimulation, down-regulated IRF3 and up-regulated IRF8 synergistically regulate the expression of MyD88 to a normal level, thus maintaining the immune balance of homeostasis and preventing serious damage from persistent over-immunization. This study presents information on Myd88–NF-κB signaling pathway in teleost fish and provides new insights into its regulatory mechanism in fish immune system.https://www.frontiersin.org/article/10.3389/fimmu.2020.00606/fullMyD88IRF3IRF8NF-κBubiquitination |
| spellingShingle | Xiaolong Yan Xiaolong Yan Xueyan Zhao Ruixuan Huo Tianjun Xu Tianjun Xu Tianjun Xu Tianjun Xu Tianjun Xu IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish Frontiers in Immunology MyD88 IRF3 IRF8 NF-κB ubiquitination |
| title | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
| title_full | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
| title_fullStr | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
| title_full_unstemmed | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
| title_short | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
| title_sort | irf3 and irf8 regulate nf κb signaling by targeting myd88 in teleost fish |
| topic | MyD88 IRF3 IRF8 NF-κB ubiquitination |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00606/full |
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